Assistant prediction and evaluation system for in-vitro fertilization pregnancy probability based on androgen reaction elasticity

Abstract

The invention discloses a system for auxiliary prediction and evaluation of an in-vitro fertilization pregnancy probability based on androgen reaction elasticity. The system comprises a data acquisition module and an androgen reaction elasticity calculation module, wherein the data acquisition module is used for acquiring the age of a subject and androgen levels at different stages; and the androgen reaction elasticity calculation module is used for calculating according to the acquired androgen levels in different stages to obtain androgen reaction elasticity parameters, and obtaining the in-vitro fertilization pregnancy probability in the ovarian stimulation period according to the androgen reaction elasticity parameters and the age of the subject.

Description

Technical Field

[0001] The present invention belongs to the technical field of auxiliary prediction and evaluation of in vitro fertilization pregnancy probability for assisted reproduction, and in particular, relates to a system for auxiliary prediction and evaluation of in vitro fertilization pregnancy probability based on androgen response elasticity. Background Art

[0002] In the field of assisted reproduction, the success rate of in vitro fertilization (IVF) treatment is closely related to the subject's ovarian response, androgen levels, and other physiological factors. In ovulation induction treatment, the GnRHa (gonadotropin-releasing hormone receptor agonist) long protocol is one of the common ovarian stimulation methods, which is used to increase the number of available mature eggs, thereby increasing the probability of successful conception. However, there are significant differences in the response of the ovaries of different patients to ovulation-inducing drugs, and ovarian function or response may be affected by hormone levels.

[0003] At present, the evaluation of ovarian function and the prediction of IVF success rate mainly rely on the age of the subjects, antral follicle count (AFC), anti-Mullerian hormone (AMH) level determination, basal follicle stimulating hormone (FSH) level determination and other methods. However, these indicators mainly reflect the ovarian reserve function, indicating that they represent the fertility differences of the group, and cannot predict the individual probability of pregnancy through ovulation induction and assisted pregnancy. For example, many literatures have found that the level of AMH cannot predict the IVF pregnancy outcome. The latest research shows that for women with AMH levels within the normal range, the dynamic changes in androgen levels can accurately predict the pregnancy outcome in the GnRHa long-term treatment. Appropriate androgen levels can promote follicular development and improve the quality of eggs, which has potential value for improving IVF results. At the same time, in the past, clinicians combined their own experience and, for subjects with normal AMH levels, mostly chose different treatment plans under the long ovulation induction program to adjust androgen levels to improve ovarian response and fertility potential based on androgen levels. There is a certain degree of subjectivity and lack of clear quantitative indicators. In summary, there is currently a lack of effective methods to assess an individual's sensitivity to androgens and their effects on ovarian function, which limits the application and development of androgen levels in the field of assisted reproduction. Summary of the invention

[0004] In order to solve the above technical problems, the present invention proposes a system for auxiliary prediction and evaluation of in vitro fertilization pregnancy probability based on androgen response elasticity to solve the problems existing in the above prior art.

[0005] In response to the above problems, the present invention proposes a new in vitro fertilization pregnancy probability auxiliary prediction and evaluation method and system, which aims to more accurately predict the IVF pregnancy probability during ovarian stimulation by evaluating the androgen response elasticity of the subject and combining the subject's age. The system is expected to provide personalized treatment advice assistance and help provide guidance and auxiliary data for optimizing treatment plans, thereby helping to improve the success rate of IVF and reduce unnecessary waste of medical resources.

[0006] To achieve the above object, the present invention provides a system for assisting prediction and evaluation of in vitro fertilization pregnancy probability based on androgen response elasticity, comprising:

[0007] A data collection module and a module for calculating androgen response elasticity; wherein the data collection module is used to collect the age of the subject and the androgen level at different stages; the module for calculating androgen response elasticity is used to calculate according to the collected androgen levels at different stages to obtain androgen response elasticity parameters, and obtain the probability of in vitro fertilization pregnancy during ovarian stimulation according to the androgen response elasticity parameters and the age of the subject.

[0008] Optionally, in the data acquisition module, the androgen levels at different stages include the testosterone level at the initial stage, the serum testosterone level when the follicle diameter is 10-12 mm, and the serum testosterone level on the day of HCG injection.

[0009] Optionally, in the module for calculating androgen response elasticity, the process of obtaining the androgen response elasticity parameter is as follows:

[0010]

[0011] Wherein, TRE1 and TRE2 represent different parameters for characterizing the androgen response elasticity of the subject, which are the first androgen response elasticity parameter and the second androgen response elasticity parameter, respectively, wherein T0 is the serum testosterone level in the initial stage, T 10-12 The diameter of the follicle is 10-12 mm. The serum testosterone level is T HCG The data are serum testosterone levels on the day of HCG injection.

[0012] Optionally, in the module for calculating androgen response elasticity, the probability of in vitro fertilization pregnancy during ovarian stimulation is obtained based on the androgen response elasticity parameter and the age of the subject, wherein the androgen response elasticity and the age of the subject are graded and assigned values, and the probability of in vitro fertilization pregnancy during ovarian stimulation is calculated based on the graded assignment results corresponding to the androgen response elasticity and the age.

[0013] Optionally, in the module for calculating androgen response elasticity, the calculation process of the IVF pregnancy probability p during ovarian stimulation is:

[0014]

[0015] Among them, Age is the graded assignment result of the subject's age; TRE1' and TRE2' are the graded assignment results of different androgen response elasticity parameters, among which β0, β1, β2 and β3 are the fitting parameters of different items, and e is a natural constant.

[0016] Optionally, in the module for calculating androgen response elasticity, the process of assigning values ​​to androgen response elasticity parameters in a graded manner includes:

[0017] The androgen response elasticity parameter is graded and assigned in four orders, and the androgen response elasticity parameter is graded and assigned in accordance with the androgen response elasticity parameter graded and assigned standard according to different values, to obtain the androgen response elasticity parameter graded and assigned result, wherein the androgen response elasticity parameter includes a first androgen response elasticity parameter and a second androgen response elasticity parameter;

[0018] The grading and assignment standards for androgen response elasticity parameters are:

[0019] When TRE1<0.5, TRE1' is 1; when TRE2<0.75, TRE2' is 1;

[0020] When 0.5≤TRE1<1.0, TRE1' is 2; when 0.75≤TRE2<1.50, TRE2' is 2;

[0021] When 1.0≤TRE1<1.5, TRE1' is 3; when 1.50≤TRE2<2.25, TRE2' is 3;

[0022] When 1.5≤TRE1, TRE1' is 4; when 2.25≤TRE2, TRE2' is 4;

[0023] Among them, TRE1 and TRE2 are the first androgen response elasticity parameter and the second androgen response elasticity parameter respectively, and TRE1' and TRE2' represent the graded assignment results corresponding to the androgen response elasticity parameters, which are the graded assignment results of the first androgen response elasticity parameter and the second androgen response elasticity parameter respectively.

[0024] Optionally, in the module for calculating androgen response elasticity, the process of assigning a graded value to age includes:

[0025] The age of the subject is graded and assigned in five levels. According to the graded and assigned standard of the age of the subject, the graded and assigned result of the age of the subject is obtained.

[0026] The age classification criteria for the subjects are:

[0027] When the subject is 30 years old or younger, Age is 0;

[0028] When the subject is older than 30 years and 35 years and younger, Age is 1;

[0029] When the subject is older than 35 years and 40 years and younger, Age is 2;

[0030] When the subject is older than 40 years and 42 years and younger, Age is 3;

[0031] When the subject is 43 years and older, Age is 4;

[0032] Among them, Age is the grading result of the subject.

[0033] Optionally, a prediction module is also included, wherein the prediction module is used to divide the probability of in vitro fertilization pregnancy during ovarian stimulation into numerical intervals, and predict the outcome of the long ovulation induction intervention protocol based on the numerical interval division result.

[0034] Optionally, in the prediction module, the prediction process of the outcome of the long ovulation induction program intervention includes:

[0035] When the IVF pregnancy probability p≥80%, it is predicted that the subject has a good outcome for the long ovulation induction program intervention;

[0036] When the IVF pregnancy probability is 65%≤p<80%, it is predicted that the subject has a good outcome of the long ovulation induction intervention;

[0037] When the IVF pregnancy probability is 50%≤p<65%, the subject is predicted to have a moderate outcome of the long ovulation induction program intervention;

[0038] When the IVF pregnancy probability p<50%, it is predicted that the subject will have a poor outcome of the long ovulation induction intervention protocol.

[0039] Compared with the prior art, the present invention has the following advantages and technical effects:

[0040] The system provided by the present invention has high prediction accuracy and does not require the subjective judgment of doctors. The system has no strict requirements on the detection method of serum testosterone, which helps to assist doctors in dealing with subjects with normal AMH and lack of other detection indicators to formulate personalized intervention methods, and assist in improving the pregnancy outcome after the long ovulation induction program intervention. In addition, the data collected by the system of the present invention are all routine mandatory inspection items of reproductive clinical institutions, excluding special inspection items or high inspection fees, which is convenient for promotion in more medical institutions. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] The drawings constituting a part of the present application are used to provide a further understanding of the present application. The illustrative embodiments and descriptions of the present application are used to explain the present application and do not constitute an improper limitation on the present application. In the drawings:

[0042] Figure 1 A schematic diagram of the system structure of an embodiment of the present invention;

[0043] Figure 2 This is a schematic diagram of the accuracy evaluation results of in vitro fertilization pregnancy outcomes based on different evaluation methods based on different data according to an embodiment of the present invention. DETAILED DESCRIPTION

[0044] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present application will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0045] It should be noted that the steps shown in the flowcharts of the accompanying drawings can be executed in a computer system such as a set of computer executable instructions, and that, although a logical order is shown in the flowcharts, in some cases, the steps shown or described can be executed in an order different from that shown here.

[0046] In view of the shortcomings of the prior art, especially for subjects with normal anti-Mullerian hormone (AMH) levels, there is a lack of a system for assisting in predicting and evaluating the probability of in vitro fertilization (IVF) pregnancy during ovarian stimulation. The system provided by the present invention particularly relates to a system for evaluating the androgen response elasticity of subjects under a long ovulation induction program and the probability of in vitro fertilization (IVF) pregnancy during ovarian stimulation. The system can be used to evaluate the androgen response elasticity level of the subject to evaluate their ovarian fertility potential; and predict the probability of in vitro fertilization (IVF) pregnancy during ovarian stimulation of the subject to evaluate whether the fertility potential of the subject is improved after the corresponding androgen response ability treatment.

[0047] The present invention first calculates the androgen response elasticity index according to the androgen levels of the subjects at different stages, and combines the age to assist in predicting the probability of in vitro fertilization (IVF) pregnancy during ovarian stimulation. Then, based on the numerical range of the default IVF pregnancy probability pre-stored in the system, an auxiliary prediction and evaluation of the outcome of the long ovulation induction intervention program for the subjects is performed to provide auxiliary suggestions for potential clinical intervention methods.

[0048] like Figure 1 Specifically, the present invention includes the following contents:

[0049] The system for auxiliary prediction and evaluation of IVF pregnancy probability includes: a data acquisition module, an androgen response elasticity calculation module;

[0050] The data collection module is used to obtain the age and androgen levels of the subjects at different stages. The androgen levels of the subjects at different stages include the initial testosterone level (T0) in the venous serum of female subjects on any day, the serum testosterone level when the follicle diameter is 10-12 mm (T 10-12 ), serum testosterone level on the day of HCG injection (T HCG );

[0051] The module for calculating androgen response elasticity (TRE) is used to calculate the above information obtained in the data acquisition module, so as to predict the androgen response elasticity (TRE) of the subject and the probability p of in vitro fertilization pregnancy during ovarian stimulation.

[0052] It should be noted that the above-mentioned system for auxiliary prediction and evaluation of in vitro fertilization pregnancy probability of the present invention is suitable for subjects with normal anti-Mullerian hormone (AMH) levels.

[0053] In the module for calculating androgen response elasticity, the androgen response elasticity is calculated based on the androgen levels at different stages obtained by the data collection module. The androgen response elasticity and age are combined to predict the probability of in vitro fertilization pregnancy p during ovarian stimulation. p is used to predict the outcome of long-term ovulation induction intervention.

[0054] In the module for calculating androgen response elasticity, data on the subject's age and androgen level at different stages are graded and assigned, and the graded assignment results are used to calculate the subject's in vitro fertilization pregnancy probability p.

[0055] In the module for calculating androgen response elasticity, the subject's age is not used directly for calculation. Instead, the subject's age is assigned a five-level grade, that is, the subject's age is divided into five levels, namely: subject's age ≤ 30, 30 < subject's age ≤ 35, 36 < subject's age ≤ 40, 40 < subject's age ≤ 42, 42 ≤ subject's age.

[0056] Re-determine the result of the graded assignment of the subject's age according to the five-level graded assignment of the subject's age.

[0057] When the subject is 30 years old or younger, Age is 0;

[0058] When the subject’s age is greater than 30 years and 35 years and below, Age is 1;

[0059] When the subject’s age was greater than 35 years and 40 years and below, Age was 2;

[0060] When the subject’s age was greater than 40 years and 42 years and below, Age was 3;

[0061] When the subject is 43 years and older, Age is 4.

[0062] In the module for calculating androgen response elasticity, data on androgen levels of subjects at different stages based on an existing multi-center database and a formula for calculating androgen response elasticity TRE are pre-stored.

[0063] The formula is as follows:

[0064]

[0065] The formula is the following formula 2:

[0066]

[0067] Wherein, TRE1 and TRE2 represent different parameters calculated for characterizing the androgen response elasticity of the subject, which are the first androgen response elasticity parameter and the second androgen response elasticity parameter, respectively, wherein T0 is the serum testosterone level in the initial stage, T 10-12 The diameter of the follicle is 10-12 mm. The serum testosterone level is T HCG The data of serum testosterone level on the day of HCG injection. The unit of testosterone level is ng / mL, which needs to be converted according to the unit of clinical test.

[0068] In the module for calculating androgen response elasticity, the androgen response elasticity of the subject is not directly used to calculate the IVF pregnancy probability, but the androgen response elasticity parameter is assigned a fourth-order grade. Among them, for different fourth-order androgen response elasticity parameters at different numerical levels, the corresponding androgen response elasticity parameter graded assignment results TRE1' and TRE2' are re-determined:

[0069] When the calculated first androgen response elasticity parameter TRE1<0.5, TRE1' is 1; when TRE2<0.75, TRE2' is 1;

[0070] When the calculated androgen response elasticity is 0.5≤TRE1<1.0, TRE1' is 2; when 0.75≤TRE2<1.50, TRE2' is 2;

[0071] When the calculated androgen response elasticity is 1.0≤TRE1<1.5, TRE1' is 3; when 1.50≤TRE2<2.25, TRE2' is 3;

[0072] When the calculated androgen response elasticity is 1.5≤TRE1, TRE1' is 4; when 2.25≤TRE2, TRE2' is 4.

[0073] Based on the above-mentioned converted parameters, the present invention provides a method for predicting the probability p of in vitro fertilization (IVF) pregnancy during ovarian stimulation of a subject under a long assisted reproductive ovulation program, and the pregnancy probability p is used to evaluate whether the fertility potential of the subject is improved after the corresponding androgen responsiveness treatment.

[0074] In the module for calculating androgen response elasticity, a formula for predicting the in vitro fertilization pregnancy probability p of a subject is pre-stored, which is fitted based on the subject's age in an existing multi-center database and the graded assignment results of the calculated androgen response elasticity TRE.

[0075] The formula is the following formula 3:

[0076]

[0077] Wherein, p is the calculated value used to characterize the probability of pregnancy in in vitro fertilization (IVF) during ovarian stimulation; Age is the graded assignment result of the subject's age; TRE1' and TRE2' are the graded assignment results of the first androgen response elasticity parameter and the graded assignment results of the second androgen response elasticity parameter, respectively, where β0, β1, β2 and β3 are fitting parameters of different items;

[0078] The fitted parameters in the association between the graded assignment results and the probability of pregnancy are:

[0079] The value space of β0 is [-0.889, 1.544]; the value space of β1 is [-1.498, -0.456]; the value space of β2 is [0.152, 1.799]; the value space of β3 is [-0.947, 0.154].

[0080] The formula for predicting the in vitro fertilization pregnancy probability p of a subject, which is fitted based on the hierarchical assignment results pre-stored based on the subject data in the existing multi-center database, has the following values: β0=0.4311; β1=-0.8956; β2=0.7938; β3=-0.2938.

[0081] The system for auxiliary prediction and evaluation of in vitro fertilization pregnancy probability of the present invention also includes a prediction module, in which a default numerical range of in vitro fertilization pregnancy probability is pre-stored, and based on the numerical range, the calculated in vitro fertilization pregnancy probability p is divided into numerical ranges or the numerical ranges are defined, so as to predict the outcome of the long ovulation induction program intervention.

[0082] In the numerical range pre-stored in the prediction module, the predicted outcome of the long ovulation induction intervention program is output according to the following standards:

[0083] When the calculated IVF pregnancy probability p for predicting the subject is ≥ 80%, the prediction module determines that the subject has an excellent outcome for the long ovulation induction program intervention;

[0084] When the calculated IVF pregnancy probability for predicting the subject is 65%≤p<80%, the prediction module determines that the subject has a good outcome of the long ovulation induction program intervention;

[0085] When the calculated IVF pregnancy probability for predicting the subject is 50%≤p<65%, the prediction module determines that the subject has a medium outcome of the long ovulation induction program intervention;

[0086] When the calculated IVF pregnancy probability p for predicting the subject is less than 50%, the prediction module determines that the subject has a poor outcome of the long ovulation induction intervention protocol.

[0087] Experimental example:

[0088] Experimental Example 1

[0089] 1. General information: A total of 109 subjects were selected from the Reproductive Center of Guangdong Provincial People's Hospital (Provincial Medical Reproductive Center) from January 2021 to December 2023 for research. Women included in this study met the following criteria: infertility; age 20-40 years old; body mass index (BMI) 18-26kg / m 2 ; serum anti-Mullerian hormone AMH>1.1ng / mL; regular natural menstrual cycles (21-35 days); fresh embryo transfer in IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) cycles through GnRH-a long protocol after controlled ovarian stimulation (COS) monitoring; and the first or second IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) cycle. Patients with any of the following were excluded: polycystic ovary syndrome or other diseases related to hyperandrogenism (such as adrenal hyperplasia, gonadal abnormalities, and pituitary lesions) and hyperprolactinemia; chromosomal abnormalities; stage III-IV endometriosis or adenomyosis; hydronephrosis confirmed by ultrasound examination; or endocrine diseases such as diabetes and thyroid dysfunction.

[0090] 2. Data collection: The following information was collected from the electronic medical records of the Provincial Hospital Reproductive Center: (1) General information: female age, anti-Mullerian hormone (AMH) level of the subjects, serum testosterone level at the initial stage (T0), serum testosterone level at the time of follicle diameter of 10-12 mm (T 10-12 ), serum testosterone level on the day of HCG injection (T HCG ) data, etc.

[0091] 3. Data analysis: This study used serum testosterone levels at different stages to calculate a new index of androgen response elasticity. Female age was re-graded into five levels. Serum testosterone and AMH factors were continuous variables. The calculated androgen response elasticity parameter index was graded into four levels. The predicted probability of IVF pregnancy p of the subject was a continuous variable, and the pregnancy outcome after long ovulation induction intervention was the prediction quality result corresponding to the four numerical intervals. The pregnancy outcomes used for model construction and verification included success and failure.

[0092] 4. Research Results

[0093] 4.1 Provide the clinical and biochemical data of the subjects under the relevant long ovulation induction protocol, as shown in Table 1.

[0094] Table 1

[0095] Provincial Medical Bureau data for the past three years (n=109) Average age (years) 31.4±3.8 AMH (ng / mL) 3.02±1.59 <![CDATA[T0]]> 1.30±0.58 <![CDATA[T 10-12 ]]> 1.51±0.69 <![CDATA[T HCG ]]> 2.27±0.95

[0096] 4.2 Calculation of androgen response elasticity

[0097] In this experimental example, the androgen response elasticity TRE1 and TRE2 of the above 109 subjects were calculated according to Formula 1 and Formula 2 respectively, and reassigned according to the fourth-order androgen response elasticity parameter grading assignment standard for calculating the subjects' in vitro fertilization pregnancy probability p.

[0098] 4.3 Fitting and calculating the IVF pregnancy probability p of the subject

[0099] In this embodiment, the ages and androgen response elasticity TRE values ​​of 109 subjects were reclassified and scored, and the values ​​used to characterize the probability of pregnancy during in vitro fertilization (IVF) during ovarian stimulation were fitted and calculated in combination with the data previously stored in the existing multi-center database and the pregnancy outcomes. The fitted parameters in the association between the classification assignment results and the probability of pregnancy were obtained as follows:

[0100] The value space of β0 is [-0.889, 1.544]; the value space of β1 is [-1.498, -0.456]; the value space of β2 is [0.152, 1.799]; the value space of β3 is [-0.947, 0.154].

[0101] In this embodiment, the values ​​of the parameters of the fitted formula for predicting the in vitro fertilization pregnancy probability p of the subject are: β0=0.4311; β1=-0.8956; β2=0.7938; β3=-0.2938.

[0102] 4.4 The outcomes of the long ovulation induction intervention protocol for 109 subjects were predicted. The results are shown in Table 2.

[0103] Table 2

[0104]

[0105]

[0106] 4.5 The accuracy of androgen response elasticity and AMH in assessing the IVF pregnancy outcomes of subjects was compared. The comparison results are shown in Table 3.

[0107] Table 3

[0108] category AUC (95% CI) AUPRC (95% CI) Age+AMH 0.58(0.41±0.75) 0.72(0.55±0.88) TRE1+TRE2 0.73(0.55±0.90) 0.71(0.55±0.93) Age+TRE1+TRE2 0.83(0.66±0.92) 0.87(0.75±0.95)

[0109] Combined with Figure 2 The accuracy evaluation results of IVF pregnancy outcomes based on different data and different evaluation methods are shown in the figure. Figure 2 A in the middle is the accuracy evaluation result of Age and AMH in assessing the in vitro fertilization pregnancy outcomes of subjects. Figure 2 B in the figure is the accuracy evaluation result of androgen response elasticity indexes TRE1 and TRE2 in assessing the in vitro fertilization pregnancy outcomes of subjects. Figure 2 C in the figure is the accuracy evaluation result of Age and androgen response elasticity indicators TRE1 and TRE2 in assessing the in vitro fertilization pregnancy outcomes of subjects. In the above evaluation results, the evaluation was performed through the receiver operating characteristic curve (ROC), where the solid line represents the corresponding receiver operating characteristic curve, the dotted line corresponds to 50% accuracy, and its AUC is the peak area under the curve.

[0110] The above results show that compared with the traditional use of AMH and age as predictive indicators of IVF pregnancy outcomes, androgen response elasticity and age are more suitable for predicting IVF pregnancy outcomes.

[0111] Experimental Example 2

[0112] 1. General information: Select patients admitted to Zhongshan First Affiliated Hospital, Zhongshan Second Affiliated Hospital and Guangdong Provincial People's Hospital Huifu Branch from June 2022 to June 2024.

[0113] A total of 151 subjects were included in the study. The women included in this study met the following criteria: infertility; age 20-40 years old; body mass index (BMI) 18-26kg / m 2; serum anti-Mullerian hormone AMH>1.1ng / mL; regular natural menstrual cycles (21-35 days); fresh embryo transfer in IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) cycles through GnRH-a long protocol after controlled ovarian stimulation (COS) monitoring; and the first or second IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) cycle. Patients with any of the following were excluded: polycystic ovary syndrome or other diseases related to hyperandrogenism (such as adrenal hyperplasia, gonadal abnormalities, and pituitary lesions) and hyperprolactinemia; chromosomal abnormalities; stage III-IV endometriosis or adenomyosis; hydronephrosis confirmed by ultrasound examination; or endocrine diseases such as diabetes and thyroid dysfunction.

[0114] 2. Data collection: The following information was collected from the electronic medical records of the Provincial Hospital Reproductive Center: (1) General information: female age, subject anti-Mullerian hormone (AMH) level, serum testosterone level at the initial stage (T0), serum testosterone level at the time of follicle diameter of 10-12 mm (T 10-12 ), serum testosterone level on the day of HCG injection (T HCG ) data, etc.

[0115] 3. Data analysis: This study used serum testosterone levels at different stages to calculate a new index of androgen response elasticity. Female age was re-graded into five levels. Serum testosterone and AMH factors were continuous variables. The calculated new index of androgen response elasticity was graded into four levels. The predicted probability of IVF pregnancy p of the subject was a continuous variable, and the pregnancy outcome after long ovulation induction intervention was a four-level graded evaluation result. The pregnancy outcomes used for model construction and verification included success and failure.

[0116] 4. Research Results

[0117] 4.1. Provide the clinical and biochemical data of the subjects under the long ovulation induction protocol, as shown in Table 4.

[0118] Table 4

[0119] Multi-center 2022-2024 data (n=151) Average age (years) 33.4±4.0 AMH (ng / mL) 2.92±1.56 <![CDATA[T0]]> 1.25±0.56 <![CDATA[T 10-12 ]]> 1.45±0.67 <![CDATA[T HCG ]]> 2.19±0.92

[0120] 4.2 The outcomes of the long ovulation induction intervention protocol for 151 subjects were predicted. The results are shown in Table 5.

[0121] Table 5

[0122]

[0123]

[0124] Experimental Example 3

[0125] 1. General information: A total of 44 subjects, including 28 cases of secondary infertility and 16 cases of primary infertility, were selected for research from January 2023 to December 2023 in the intervention study of the inventor team of Guangdong Provincial People's Hospital. Women included in this study met the following criteria: infertility; age 20-40 years old; body mass index (BMI) 18-26kg / m 2 ; serum anti-Mullerian hormone AMH>1.1ng / mL; regular natural menstrual cycles (21-35 days); fresh embryo transfer in IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) cycles through GnRH-a long protocol after controlled ovarian stimulation (COS) monitoring; and the first or second IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) cycle. Patients with any of the following were excluded: polycystic ovary syndrome or other diseases related to hyperandrogenism (such as adrenal hyperplasia, gonadal abnormalities, and pituitary lesions) and hyperprolactinemia; chromosomal abnormalities; stage III-IV endometriosis or adenomyosis; hydronephrosis confirmed by ultrasound examination; or endocrine diseases such as diabetes and thyroid dysfunction.

[0126] 2. Data collection: The following information was collected from the electronic medical records of the Provincial Hospital Reproductive Center: (1) General information: female age, subject anti-Mullerian hormone (AMH) level, serum testosterone level at the initial stage (T0), serum testosterone level at the time of follicle diameter of 10-12 mm (T 10-12 ), serum testosterone level on the day of HCG injection (T HCG ) data, etc.

[0127] 3. Data analysis: This study used serum testosterone levels at different stages to calculate a new index of androgen response elasticity. Female age was re-graded into five levels. Serum testosterone and AMH factors were continuous variables. The calculated androgen response elasticity parameter index was graded into four levels. The predicted probability of IVF pregnancy p of the subject was a continuous variable, and the pregnancy outcome after long ovulation induction intervention was the prediction quality result corresponding to the four numerical intervals. The pregnancy outcomes used for model construction and verification included success and failure.

[0128] 4. Research Results

[0129] 4.1 Calculation of androgen response elasticity

[0130] In this embodiment, the androgen response elasticity TRE1 and TRE2 of the above 44 subjects are calculated according to Formula 1 and Formula 2, respectively, and converted according to the fourth-order graded assignment standard for calculation of the subjects' in vitro fertilization pregnancy probability p.

[0131] 4.2 Fitting and calculating the IVF pregnancy probability p of the subject

[0132] In this embodiment, the values ​​of the formula parameters for predicting the in vitro fertilization pregnancy probability p of the subject are: β0=0.4311; β1=-0.8956; β2=0.7938; β3=-0.2938.

[0133] 4.3. Provide the clinical and biochemical data of the subjects under the long ovulation induction protocol, as shown in Table 6.

[0134] Table 6

[0135] Secondary infertility (n=28) Primary infertility (n=16) Average age (years) 33.1±4.1 33.9±3.8 <![CDATA[T0]]> 0.35±0.14 0.48±0.15 <![CDATA[T 10-12 ]]> 0.48±0.21 0.54±0.20 <![CDATA[T HCG ]]> 0.68±0.27 0.71±0.25

[0136] 4.4 Predicted the outcomes of the long ovulation induction intervention protocol for 44 subjects. The results are shown in Table 7.

[0137] Table 7

[0138] category Predicting the success rate of intervention outcomes Secondary infertility (n=28) 56.6％ Primary infertility (n=16) 100％

[0139] The above are only preferred specific implementations of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed in the present application should be included in the protection scope of the present application. Therefore, the protection scope of the present application should be based on the protection scope of the claims.

Claims

1. A system for assisting prediction and evaluation of in vitro fertilization pregnancy probability based on androgen response elasticity, characterized in that: include: Data collection module and androgen response elasticity calculation module; The data collection module is used to collect the age of the subject and the androgen level at different stages; the androgen response elasticity calculation module is used to calculate according to the collected androgen levels at different stages to obtain the androgen response elasticity parameter, and the probability of in vitro fertilization pregnancy during ovarian stimulation is obtained according to the androgen response elasticity parameter and the age of the subject.

2. The system according to claim 1, characterized in that In the data acquisition module, the androgen levels at different stages include the testosterone level at the initial stage, the serum testosterone level when the follicle diameter is 10-12 mm, and the serum testosterone level on the day of HCG injection.

3. The system according to claim 1, characterized in that In the module for calculating androgen response elasticity, the process of obtaining the androgen response elasticity parameter is as follows: Wherein, TRE1 and TRE2 represent different parameters for characterizing the androgen response elasticity of the subject, which are the first androgen response elasticity parameter and the second androgen response elasticity parameter, respectively, wherein T0 is the serum testosterone level in the initial stage, T 10-12 The diameter of the follicle is 10-12 mm. The serum testosterone level is T HCG The data are serum testosterone levels on the day of HCG injection.

4. The system according to claim 1, characterized in that In the module for calculating androgen response elasticity, the probability of in vitro fertilization pregnancy during ovarian stimulation is obtained according to the androgen response elasticity parameter and the age of the subject, wherein the androgen response elasticity and the age of the subject are graded and assigned, and the probability of in vitro fertilization pregnancy during ovarian stimulation is calculated according to the graded assignment results corresponding to the androgen response elasticity and the age.

5. The system according to claim 4, characterized in that In the module for calculating androgen response elasticity, the calculation process of the IVF pregnancy probability p during ovarian stimulation is: Among them, Age is the graded assignment result of the subject's age; TRE1' and TRE2' are the graded assignment results of different androgen response elasticity parameters, among which β0, β1, β2 and β3 are the fitting parameters of different items, and e is a natural constant.

6. The system according to claim 4, characterized in that In the androgen response elasticity calculation module, the process of assigning values ​​to androgen response elasticity parameters in a graded manner includes: The androgen response elasticity parameter is graded and assigned in four orders, and the androgen response elasticity parameter is graded and assigned in accordance with the androgen response elasticity parameter graded and assigned standard according to different values, to obtain the androgen response elasticity parameter graded and assigned result, wherein the androgen response elasticity parameter includes a first androgen response elasticity parameter and a second androgen response elasticity parameter; The grading and assignment standards for androgen response elasticity parameters are: When TRE1<0.5, TRE1' is 1; when TRE2<0.75, TRE2' is 1; When 0.5≤TRE1<1.0, TRE1' is 2; when 0.75≤TRE2<1.50, TRE2' is 2; When 1.0≤TRE1<1.5, TRE1' is 3; when 1.50≤TRE2<2.25, TRE2' is 3; When 1.5≤TRE1, TRE1' is 4; when 2.25≤TRE2, TRE2' is 4; Among them, TRE1 and TRE2 are the first androgen response elasticity parameter and the second androgen response elasticity parameter respectively, and TRE1' and TRE2' represent the graded assignment results corresponding to the androgen response elasticity parameters, which are the graded assignment results of the first androgen response elasticity parameter and the second androgen response elasticity parameter respectively.

7. The system according to claim 4, characterized in that In the module for calculating androgen response elasticity, the process of assigning grades to age includes: The age of the subject is graded and assigned in five levels. According to the graded and assigned standard of the age of the subject, the graded and assigned result of the age of the subject is obtained. The age classification criteria for the subjects are: When the subject is 30 years old or younger, Age is 0; When the subject is older than 30 years and 35 years and younger, Age is 1; When the subject is older than 35 years and 40 years and younger, Age is 2; When the subject is older than 40 years and 42 years and younger, Age is 3; When the subject is 43 years and older, Age is 4; Among them, Age is the grading result of the subject.

8. The system according to claim 1, characterized in that It also includes a prediction module, wherein the prediction module is used to divide the probability of in vitro fertilization pregnancy during ovarian stimulation into numerical intervals, and predict the outcome of the long ovulation induction program intervention based on the numerical interval division results.

9. The system according to claim 1, characterized in that In the prediction module, the prediction process of the outcome of the long ovulation induction program intervention includes: When the IVF pregnancy probability p≥80%, it is predicted that the subject has a good outcome for the long ovulation induction program intervention; When the IVF pregnancy probability is 65%≤p<80%, it is predicted that the subject has a good outcome of the long ovulation induction intervention; When the IVF pregnancy probability is 50%≤p<65%, the subject is predicted to have a moderate outcome of the long ovulation induction program intervention; When the IVF pregnancy probability p<50%, it is predicted that the subject will have a poor outcome of the long ovulation induction intervention protocol.

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